Abstract
Rationale
In psychiatric clinical practice, there is a need to identify psychotropic drugs whose metabolisms are prone to be altered with increased inflammatory activity in an individual patient.
Objectives
The aim of this study was to find out whether elevated serum levels (≥5 mg/l) of C-reactive protein (CRP), an established laboratory marker of infection and inflammation, are associated with increased serum concentrations of the atypical antipsychotic drugs clozapine, quetiapine, and risperidone.
Methods
Therapeutic drug monitoring request forms of patients whose antipsychotic drug concentrations had been measured under conditions of normal (<5 mg/l) and pathological (>5 mg/l) levels of C-reactive protein were retrospectively screened. The serum concentrations in relation to the daily doses [concentration per dose (C/D) (ng/mL/mg)] and the metabolic ratios [ratio of concentrations (metabolite/drug)] were compared intraindividually by the Wilcoxon signed rank test. To the study effects of the intensity of infections on drug concentrations, C-reactive protein and C/D levels were submitted to Spearman’s correlation analysis.
Results
Elevated levels of C-reactive protein were found in 105 patients. They were significantly associated with elevated values in C/D for clozapine (n = 33, P < 0.01) and risperidone (n = 40, P < 0.01). A trend for an increase was found for quetiapine (n = 32, P = 0.05). Median increases were 48.0 % (clozapine), 11.9 % (quetiapine), and 24.2 % (active moiety of risperidone), respectively.
Conclusions
In patients who exhibit signs of inflammation or infection with increased C-reactive protein values during psychopharmacological treatment, especially under clozapine and risperidone, therapeutic drug monitoring is recommendable in order to minimize the risk of intoxications due to elevated drug concentrations.
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Acknowledgments
The authors wish to thank Hans-Garlich Struss, Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, who extracted patients with high CRP levels from the data base.
Conflict of interest
Christoph Hiemke has received speaker’s or consultancy fees from the following pharmaceutical companies: Astra Zeneca, Janssen-Cilag, Pfizer, Lilly, and Servier. He is managing director of the psiac GmbH which provides an Internet-based drug-drug interaction program for psychopharmacotherapy. He reports no conflict of interest with this publication. Gudrun Hefner has received speaker’s fee from Servier. She reports no conflict of interest with this publication. All other authors declare no conflicts of interest as well. The research study did not receive funds or support from any source.
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Hefner, G., Shams, M.E.E., Unterecker, S. et al. Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels. Psychopharmacology 233, 1695–1705 (2016). https://doi.org/10.1007/s00213-015-3976-0
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DOI: https://doi.org/10.1007/s00213-015-3976-0